- 期刊
Evaluation of DNA-Binding Ability of Antibiotic DC-81 - Indole Conjugates by Restriction Endonuclease BamHI and Molecular Modeling Studies
並列摘要
DC-81 (I), an antitumor antibiotic produced by Streptomyces species, belongs to the pyrrolo-[2,1-c][l,4]benzodiazepines (PBDs) which are potent inhibitors of nucleic acid synthesis because of their ability to recognize and bind to specific sequence of DNA to form a labile covalent adduct. The hybrid agents comprised of DC-81 (l) and indole carboxylate (IC) moiety 2 through carbon chain linkers (comprised of zero and two to four carbons) have been designed and synthesized by our group. These compounds with DNA binding ability were determined by restriction endonuclease BamHI and molecular modeling studies. The results demonstrated that DC-81 – IC hybrid 3c (with a three carbon chain linker) showed a higher DNA-binding affinity and gave rise to a maximal stabilization of the complex with DNA at the minor groove as compared to the other complexes formed with 3a, 3b and 3d.